Combination of cuprizone and experimental autoimmune encephalomyelitis to study inflammatory brain lesion formation and progression

Autor: Miriam Scheld, Stella Nyamoya, Sven Olaf Rohr, Tim Clarner, Tanja Hochstrasser, Tine Swartenbroekx, Peter Ponsaerts, Chloé Hoornaert, Christoph Schmitz, Daniela Dreymueller, Lars-Ove Brandenburg, Bernhard Josef Rüther, Markus Kipp, Cordian Beyer, Uta Chrzanowski, Petra Fallier-Becker, Eugenia Kress
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
Pathology
medicine.medical_specialty
Encephalomyelitis
Autoimmune
Experimental
Receptors
CCR2
Freund's Adjuvant
Gene Expression
Inflammation
Mice
Transgenic
Grey matter
Biology
Monocytes
Receptors
Interleukin-8A
White matter
03 medical and health sciences
Cellular and Molecular Neuroscience
Amyloid beta-Protein Precursor
Mice
0302 clinical medicine
Glial Fibrillary Acidic Protein
medicine
Animals
ddc:610
Glia limitans
Microglia
Multiple sclerosis
Experimental autoimmune encephalomyelitis
medicine.disease
Intercellular Adhesion Molecule-1
Peptide Fragments
Mice
Inbred C57BL
Disease Models
Animal
Luminescent Proteins
030104 developmental biology
medicine.anatomical_structure
Neurology
Forebrain
Disease Progression
Encephalitis
Female
Myelin-Oligodendrocyte Glycoprotein
Human medicine
medicine.symptom
Sesquiterpenes
030217 neurology & neurosurgery
Zdroj: Glia
ISSN: 0894-1491
Popis: Brain-intrinsic degenerative cascades are a proposed factor driving inflammatory lesion formation in multiple sclerosis (MS) patients. We recently described a model combining noninflammatory cytodegeneration (via cuprizone) with the classic active experimental autoimmune encephalomyelitis (Cup/EAE model), which exhibits inflammatory forebrain lesions. Here, we describe the histopathological characteristics and progression of these Cup/EAE lesions. We show that inflammatory lesions develop at various topographical sites in the forebrain, including white matter tracts and cortical and subcortical grey matter areas. The lesions are characterized by focal demyelination, discontinuation of the perivascular glia limitans, focal axonal damage, and neutrophil granulocyte extravasation. Transgenic mice with enhanced green fluorescent protein-expressing microglia and red fluorescent protein-expressing monocytes reveal that both myeloid cell populations contribute to forebrain inflammatory infiltrates. EAE-triggered inflammatory cerebellar lesions were augmented in mice pre-intoxicated with cuprizone. Gene expression studies suggest roles of the chemokines Cxcl10, Ccl2, and Ccl3 in inflammatory lesion formation. Finally, follow-up experiments in Cup/EAE mice with chronic disease revealed that forebrain, but not spinal cord, lesions undergo spontaneous reorganization and repair. This study underpins the significance of brain-intrinsic degenerative cascades for immune cell recruitment and, in consequence, MS lesion formation.
Databáze: OpenAIRE
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